POLARCREST

We propose here to investigate new mechanisms whereby key cellular pathways including cellular polarization, hypoxia and energetic status regulate NCC proliferation, migration and pluripotency. Questioning the role of these processes has never been undertaken during the ontogeny of NC-derived structures, so far. We postulate that the crucial contribution of the cephalic NC to the facial structures and the cephalic development tightly relies on LKB1 pathway. The aim of our project is to investigate the extent to which, LKB1 control energetic status and metabolism of the cephalic NCC and influence the behavior of NCC, their fate and contribution to face development and brain morphogenesis. To address these questions, classical conditional transgenic appoaches in mice are not appropriate. Gene manipulations alone are meaningless without a thorough investigation of in vivo cell lineages. For this reason, we will work with embryonic chimeras as model. The use of embryonic chimeras (chick-quail transplantation) is a powerful and conclusive technique to determine the function of discrete cell populations during embryonic development (Le Douarin, 1969). The embryonic chimeras can still reveal totally novel and fundamental insights into the cellular mechanisms of embryonic development. Based on species-specific heritable cellular labeling, the fate of embryonic cells can be traced throughout ontogenetic processes. It serves as the standard for all ensuing molecular investigations of the underlying regulatory circuitry. It enables to look at the right genes inside the right cells that are signaling to each other in appropriately defined time windows.